Rheumatoid factors are antiglobulin antibodies that bind heterogeneous determinants on the crystallizable fragment (Fc) of IgG immunoglobulins and are found in the serum and synovial fluid of most patients with rheumatoid arthritis. The role of rheumatoid factors in the pathogenesis of rheumatoid arthritis has been questioned because they are also present in patients with various other chronic diseases, suggesting that their presence is non-specific. However, the binding specificity of rheumatoid factors is diverse and includes allotypic antigens (Gm) on human IgG, neoantigens created within IgG by the formation of the immune complexes, and crossreactive antigens shared by other mammalian IgG immunoglobulins.
Rheumatoid factors that bind alloantigens may occur as a result of blood transfusions and pregnancy, but they do not represent true autoantibodies unless they bind self determinants. Rheumatoid factors that bind neoantigens are also not true autoantibodies, as they are directed to new determinants formed within immune complexes. In contrast, the presence of an autologous reactive rheumatoid factor specificity, Ga, in rheumatoid serum has been demonstrated.
The presence of autoreactive rheumatoid factors in circulating immune complexes from patients with rheumatoid arthritis supports a potential pathogenic role for these autoantibodies. However, the method currently used to detect rheumatoid factors does not exclusively identify the presence of autoreactive antibodies. Moreover, techniques to measure disease related rheumatoid factor autoantibodies are too complex to permit an evaluation of their specificity for rheumatoid arthritis. It is therefore of great interest to be able to develop techniques which have significant specificity for rheumatoid arthritis.